The Apicomplexa is a diverse phylum of protozoa containing some of the most pathogenic organisms known to man. Representatives include taxa of the well known genera such as Plasmodium, Babesia and Toxoplasma. In 1984 a research group in Norway reported a previously unknown cyst-forming protozoan which caused encephalitis and myositis in dogs (Bjerkas et al. 1984). These clinical signs were consistent with those caused by Toxoplasma gondii, a widely distributed member of the Apicomplexa. However, unlike T. gondii, the organism was not pathogenic to outbred mice, nor were T. gondii specific antibodies present in the sera of the dogs studied. This prompted further investigation which demonstrated conclusively the organism was ultrastructurally and antigenically distinct from T. gondii (Dubey et al 1988). Neospora caninum was thus described as a new member of the Sarcocystidae. Soon after, N. caninum was implicated as a cause of abortion in cattle (Thilstead & Dubey, 1989).
An increasing number of N. caninum isolates have now been obtained, using techniques involving predominantly the direct inoculation of infected tissues onto tissue culture cells (Dubey et al. 1988, Conrad et al. 1993), although bovine isolates have proven difficult to obtain. The primary reason for this has been the detrimental effects of autolysis on the viability of N. caninum in aborted bovine fetal tissues. The isolation of a parasite population from a live animal is therefore preferred.
Recent studies on the biological properties of bovine and canine isolates have suggested they belong to a single species called N. caninum (Holmdahl et al. 1997), despite the record that wide differences exist between isolates in their biological properties. These include differences in antigenicity, ultrastructure, pathogenicity and genetic heterogeneity (Conrad et al. 1993, Marsh et al. 1995, Lindsay et al. 1995 and Atkinson et al. 1999). Thus not all isolates of N. caninum may possess the same properties, and indeed at least one isolate of N. caninum was mistakenly identified as Hammondia heydorni previously (Schares et al. 2001). Indeed, others have speculated on whether N. caninum and H. heydorni are the same or different species (Mehlhorn and Heydorn, 2000). Hammondia heydorni is also a cyst-forming coccidian that has a life cycle which is very similar to that of N. caninum. Thus the true identity of the species N. caninum is currently being debated, and its relationship to H. heydorni is unclear.
In cattle, abortion due to N. caninum infections usually occur in mid- to late gestation, although not all infected foetuses are aborted. Many congenitally infected calves are born healthy and persistently infected, although some infected calves are diseased at birth and die in the neonatal period with lesions similar to those of aborted calves.
The development and use of serological tests for the diagnosis of neosporosis in livestock, along with the identification of animals infected or exposed to N. caninum, has been reviewed previously in great detail (Bjorkman et al. 1999; Atkinson et al. 2000a). Significantly, however, there is no effective vaccine against transplacental transmission or foetal loss which occurs as a result of neosporosis and attempts to formulate a vaccine have met with limited success.
Liddel et al. (1999) injected female BALB/c mice with a crude N. caninum tachyzoite lysate preparation co-administered with ImmuMAXSR™ adjuvant. These mice were subsequently mated, and pregnant dams were challenged with N. caninum tachyzoites at 10-12 days of gestation. Results showed a single injection offered complete protection against transplacental transmission of the parasite to the pups. All pups in this experimental group were free from parasitic infection. No results have yet been reported on the efficacy of this vaccine formulation in the bovine.
Baszler et al. (2000) examined the possibility of vaccination of BALB/c mice with soluble N. caninum antigen formulated in either nonionic surfactant vesicles or Freunds Complete Adjuvant. This approach resulted in exacerbation of encephalitis and neurological disease in these mice. These observations were characterised by increased antigen specific IL-4 secretion and increased IgG1:IgG2a ratios in vivo.
Adrianarivo et al. (1999) tested four different adjuvants with a killed whole N. caninum tachyzoite preparation for immunogenicity. The results indicated that the immune responses, as determined by IFAT titres, were significantly higher in experimentally infected cattle compared to immunised cattle.
Adrianarivo et al. (2000) studied the effect of a killed N. caninum tachyzoite preparation in pregnant cattle using a POLYGEN™ adjuvant. Heifers were injected at day 35 and day 65 of gestation and four weeks later were challenged with intravenous or intramuscular injection of tachyzoites. Post immunisation, heifers developed both humoral and cell mediated immune responses characterised by an increase in production of IgG1 and IFN-γ respectively. Following a challenge with N. caninum tachyzoites, however, significant cell mediated immune response did not occur. All foetuses in the study, both from control and experimental cattle, developed lesions characteristic of N. caninum infection. Failure to prevent foetal infection by this formulation in pregnant cattle was concluded.
Unlike the development of killed or genetically engineered vaccines against parasites, vaccines based on live populations of parasites are available, for example against Toxoplasma-induced abortion in sheep (Buxton & Innes, 1995) and Eimeria parasites of poultry (Shirley & Bedrnik, 1997). A live vaccine is not, however, available against N. caninum. 
The literature on live vaccines against N. caninum is limited. Atkinson et al. (1999) showed that infection of naive mice by the Nc-SweB1 isolate of N. caninum partially protected them against a severe infection by Nc-Liverpool. Lindsay et al. (1999) generated temperature sensitive mutants of N. caninum and demonstrated that they could prevent clinical signs associated with neosporosis in mice.